The primary objective of the work effort has been to develop sensitive analytical techniques for the determiniation of cocaine and its metabolites in all types of biologic fluids. A primary approach has been to evaluate numerous solvent systems for an enhanced efficiency in extracting cocaine metabolites, particularly benzoyl ecgonine, from biologic specimens. It was observed that a chloroform: ethanol (90:10) solvent mixture removed approximately 80% of the benzoyl ecgonine from urine. Additionally the recovery of the cocaine metabolite can be substantially increased by salting out the benzoyl ecgonine with anhydrous sodium sulfate. This modification increased the recovery to approximately 96%. The development and evaluation of a gas-liquid chromatographic (GLC) procedure for determining benzoyl ecgonine in urine has also been achieved. The technique involves the conversion of extracted benzoyl ecgonine to cocaine by means of a methylation reaction at a yield of 84%. The much less polar cocaine is subsequently chromatographed with relative ease. The procedure (GLC) is reproducible with a coefficient of variation of approximate 3%. Sensitivity approaches 0.2 micrograms/ml for 5 ml of urine and a single technician can perform 20-25 analyses per day. Time requirements prevent the procedure from being applicable to large-scale screening of drug abusers. A current approach is to derivatize benzoyl ecgonine to products that can be detected on thin-layer chromatography with high levels of sensitivity. Under this project methods have also been developed for determining morphine and amitriptyline in small amounts of serum.